Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
Robert John Motzer ◽  
Carlos H. Barrios ◽  
Tae Min Kim ◽  
Silvia Falcon ◽  
Thomas Cosgriff ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Phase Ii Trial ◽  
Primary Objective ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
End Points ◽  
Treatment Paradigm

4504 Background: Sequential SUN (tyrosine kinase inhibitor, TKI) until progression of disease (PD) followed by EVE (mTOR inhibitor) is standard therapy for patients with mRCC. This open-label, multicenter, phase II trial compared 1st-line EVE to 1st-line SUN (NCT00903175). Sequential EVE→SUN was also compared with standard SUN→EVE. Methods: Patients with mRCC (clear or non-clear cell) naive to prior systemic therapy were randomized 1:1 to either 1st-line EVE 10 mg/day or SUN 50 mg/day (4 weeks on, 2 weeks off) until PD. Patients then crossed over and continued on the alternate drug until PD. Primary objective was to assess PFS noninferiority of 1st-line EVE to 1st-line SUN; defined as an observed hazard ratio (HR)1st EVE/SUN ≤1.1. Overall survival (OS), combined 1st-line and 2nd-line PFS, and safety were secondary end points. Results: From10/09 to 6/11, 471 patients enrolled (EVE→SUN, n = 238; SUN→EVE, n = 233). Median age was 62 years, 85.4% had clear-cell RCC, and MSKCC favorable/intermediate/poor risk was 30/56/14%. Median follow-up was 22.7 months. A total of 53.7% of patients who discontinued 1st-line EVE entered into 2nd-line SUN and 51.6% of patients who discontinued 1st-line SUN entered into 2nd-line EVE. Median PFS (95% CI) was 7.9 (5.6-8.2) months for 1st-line EVE and 10.7 (8.2-11.5) months for 1st-line SUN. HR1st EVE/1st SUN (95% CI) was 1.43 (1.15-1.77). Median OS (95% CI) was 22.4 (19.7-NA) months for EVE→SUN and 32.0 (20.5-NA) months for SUN→EVE; HREVE-SUN/SUN-EVE (95% CI) was 1.24 (0.94-1.64). A trend in favor of SUN→EVE for OS was observed, but will need to be confirmed with final OS analysis. Additional efficacy results for secondary end points are forthcoming. Common treatment-emergent adverse events for 1st-line EVE vs SUN, respectively, were stomatitis (53% vs 57%), fatigue (45% vs 51%), and diarrhea (38% vs 57%). Conclusions: Noninferiority of PFS for 1st-line EVE compared with SUN was not achieved in this randomized phase II trial of mRCC patients. The treatment paradigm remains SUN→EVE since the sequence achieved optimal clinical benefit. Clinical trial information: NCT00903175.

Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naïve patients with metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
B. Escudier ◽  
C. Szczylik ◽  
T. Demkow ◽  
M. Staehler ◽  
F. Rolland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Prognostic Score ◽  
Primary Objective ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

4501 Background: Sorafenib, an oral multi-kinase inhibitor that targets tumor growth and vascularization, significantly prolonged PFS in a Phase III trial with previously treated mRCC patients. This randomized Phase II trial investigated the efficacy and tolerability of sorafenib compared with IFN in first-line therapy of patients with clear-cell RCC. Methods: Untreated patients with mRCC were stratified by MSKCC prognostic score and randomized to receive continuous oral sorafenib 400 mg bid or IFN 9 million units tiw, with an option of dose escalation (600 mg bid sorafenib) or crossover from IFN to sorafenib upon disease progression. The study assessed PFS at 99 events as primary objective, best response (RECIST), overall survival, health-related quality of life, and adverse events (AEs). Results: Baseline characteristics of 188 patients (sorafenib n=97; IFN n = 91) were: median age 62.0 years; MSKCC score: 57% low, 41% intermediate, 1% high; prior nephrectomy: 82%; ECOG 0:1, 55.3%:44.7%. As of January 6, 2006, PFS events have been reported for 64 (34%) patients. Preliminary data showed drug-related AEs of any severity (sorafenib vs IFN) in 50.5% vs 51.6% of patients (≥grade 3: 8.2% vs 11.0%), including diarrhea (24.7% vs 5.5%), fatigue (14.4% vs 20.9%), fever (2.1% vs 18.7%), hypertension (13.4% vs 0%), nausea (5.2% vs 13.2%), flu-like syndrome (1.0% vs 6.6%), hand-foot skin reaction (6.2% vs 0%), and rash/desquamation (4.1% vs 0%). Drug-related metabolic/laboratory abnormalities at grade 3 (no grade 4) comprised hypophosphatemia (21.7% vs. 0%), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%) and hypoalbuminemia (0% vs. 3.6%). Five patients receiving IFN withdrew from treatment due to AEs, whereas only one patient withdrew from sorafenib. Conclusions: Sorafenib was generally well tolerated in RCC patients in the first-line setting, with relatively infrequent drug-related AEs ≥grade 3. Full PFS data will be presented at the meeting. [Table: see text]

Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: Results from a multicenter, open-label, single-arm, phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16199-e16199
Author(s):  
Lin Shen ◽  
Xianjun Yu ◽  
Ming Lu ◽  
Xing Zhang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Neuroendocrine Carcinoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Grade 3

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

Anlotinib Plus Toripalimab and Nab-Paclitaxel in Patients with Locally Advanced or Metastatic Pancreatic Cancer: Study Protocol for An Open-Label, Non-Randomized, Phase II Study (ATNPA)

2021 ◽  
Author(s):  
Jingwen Chen ◽  
Yiqian Liu ◽  
Yizhi Zhu ◽  
Shiyun Cui ◽  
Chongqi Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Maintenance Therapy ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Combination Strategy

Abstract Background There have not been standard second-line or maintenance regimens with definite survival benefits so far for patients with pancreatic carcinoma who have lost the opportunity of curable resections or failed first-line chemotherapy. Anlotinib, a potent small-molecule tyrosine kinase inhibitor, exhibits anti-angiogenic and anti-tumour effects by specifically binding to multiple targets such as VEGFR, FGFR, PDGFR, c-Kit and Ret. Toripalimab, a novel anti-PD-1 mAb, has been proved to significantly prolong progression-free survival (PFS) and overall survival (OS) in various solid tumours with manageable toxicities when combining with cytotoxic chemotherapy. We design this study to assess the combination of anlotinib, toripalimab and nab-paclitaxel as a second-line or maintenance therapy for locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC). Patients and Methods: This is an open-label, non-randomized, single-arm phase Ⅱ study, aimed at evaluating the efficacy and safety profile of the above-mentioned combination strategy in first-line therapy-failed LAPC or MPC. Totally 53 patients are to be enrolled and receive anlotinib (12 mg, po. qd.) plus toripalimab (240 mg, ivgtt. q3w.) and nab-paclitaxel (125 mg/m2, ivgtt, d1, d8) every 3 weeks as a cycle until disease progression or intolerable adverse events. The primary endpoint is PFS. Secondary end points include OS, disease control rate (DCR), object response rate (ORR), quality of life (QoL) and safety. Enrollment started in April 2021, and follow-up will be finished in April 2023. Discussion and Significance: Combination of anlotinib, toripalimab and nab-paclitaxel may promote vessel normalization and drug delivery, and activate the immune response, thus exerting synergistic anti-tumour effects and counteracting the immunosuppressive microenvironment of pancreatic cancer. As the first intending to assess this combination in pancreatic cancer, this study will provide comprehensive evidence for second-line or maintenance therapy of LAPC and MPC. Trial registration: ClinicalTrials.gov: ATNPA, NCT04718701. Registered January 22, 2021. (https://clinicaltrials.gov/ct2/show/NCT04718701?term=NCT04718701&draw=2&rank=1)

scholarly journals Capecitabine plus Oxaliplatin as a Second-Line Therapy for Advanced Biliary Tract Cancers: A Multicenter, Open-Label, Phase II Trial

2019 ◽  
Vol 10 (25) ◽  
pp. 6185-6190
Author(s):  
Seung Tae Kim ◽  
Sung Yong Oh ◽  
Jeeyun Lee ◽  
Jung Hun Kang ◽  
Hyun Woo Lee ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Biliary Tract Cancers ◽  
Line Therapy ◽  
Open Label Phase

scholarly journals Phase II Randomized Trial Comparing Sequential First-Line Everolimus and Second-Line Sunitinib Versus First-Line Sunitinib and Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma

2014 ◽  
Vol 32 (25) ◽  
pp. 2765-2772 ◽  
Author(s):  
Robert J. Motzer ◽  
Carlos H. Barrios ◽  
Tae Min Kim ◽  
Silvia Falcon ◽  
Thomas Cosgriff ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Second Line ◽  
First Line ◽  
First Line Therapy

Purpose A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma. Patients and Methods RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety. Results Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively). Conclusion Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

Phase II study of ifosfamide, carboplatin and etoposide (ICE) in recurrent glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2066-2066
Author(s):  
T. Aoki ◽  
K. Nojima ◽  
T. Mizutani ◽  
M. Ishikawa ◽  
A. Takasu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Secondary Endpoints

2066 Background: To evaluate the efficacy and tolerability of ifosfamide, carboplatin and etoposide ( ICE ) in patients with recurrent glioblastoma. Methods: This was an open-label, single-center phase II trial. Forty-two patients with first recurrent glioblastoma after surgery, standard radiotherapy and a first-line temozolomide-based or ACNU-based chemotherapy, were enrolled.The primary endpoint was progression-free survival at 6 months ( PFS-6 ), and secondary endpoints were response rate, toxicity, and survival. Chemotherapy consisted of Ifosfamide ( 700 mg / m2 on day 1, 2 and 3 ), carbopaltin ( 100 mg / m2 on day 1 ), etoposide ( 70 mg / m2 on day 1, 2, and 3 ), every 6 weeks. Results: PFS-6 was 37 %. The median PFS was 17 weeks. Response rate was 27 %. Adverse events were generally mild ( grade 1 or 2 ) and consisted mainly of alopecia. Conclusions: This regimen is well tolerated and has activity in patients with recurrent glioblastoma. No significant financial relationships to disclose.

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